Vertebrate PCP components and modulators, their role in PCP signaling, and their involvement in cancer
| Gene | Structure | Function in PCP | Involvement in cancer |
|---|---|---|---|
| Upstream PCP components | |||
| Wnt 5a,11 | Secreted glycoprotein | Initiate PCP signaling | Promote or inhibit cancer (context dependent) |
| Fat | Protocadherin | Cell adhesion and signaling | Deletion or silencing in oral squamous carcinoma |
| Dachsous | Protocadherin | Cell adhesion and signaling | Tumor suppressor gene |
| Four-jointed | Golgi kinase | Phosphorylate cadherin domains of Fat and Dachsous | Unknown |
| Atrophin | Transcriptional corepressor | Bind cytoplasmic tail of Fat | Altered expression in neuroblastoma |
| Core PCP components | |||
| Frizzled | 7-Transmembrane receptor | Recruit Dvl to membrane upon binding Wnt | Upregulated in cancer |
| Dishevelled | Cytoplasmic protein | Recruited to membrane by Fzd | Upregulated in cancer |
| Vangl | 4 -Transmembrane protein | Bind Dvl and PKCδ | High expression in metastatic tissue |
| Celsr | 7-Transmembrane protocadherin | Regulate asymmetrical localization of Fzd | Unknown |
| Prickle | Cytoplasmic protein | Antagonize Dvl recruitment by Fzd | Downregulated in hepatocellular carcinoma |
| Downstream PCP effectors | |||
| Daam1 | Formin | Bridge Dvl and RhoA | Unknown |
| RhoA | Small GTPase | Regulate cytoskeleton downstream of Daam1 | Upregulated in cancer |
| Rac | Small GTPase | Regulate cytoskeleton downstream of Dvl | Upregulated in cancer |
| JNK | S/T protein kinase | Regulate cytoskeleton downstream of Rac | Upregulated in cancer |
| Rock | Rho kinase | Regulate cytoskeleton downstream of Rho | Upregulated in cancer |
| Profilin | G-actin-binding protein | Bind DAAM1 | Low expression in breast, pancreatic, and hepatic cancer |
| PCP Modulators | |||
| Paraxial protocadherin | Protocadherin | Promote Dvl recruitment to membrane | Downregulated in breast cancer |
| EphrinB1 | Transmembrane ligand for Eph | Bind Dvl and activate Rho | Promote cancer cell invasion |
| PKCδ | PKC kinase | Bind and activate Dvl for membrane recruitment | Breast cancer progression |
| Sprouty1 | Cytoplasmic protein | Inhibit Dvl recruitment to membrane | Tumor suppressor gene |
| Cthrc1 | Secreted glycoprotein | Form Cthrc1-Wnt-Fzd complex to promote PCP | Upregulated in invasive cancer |
| Ptk7 | Transmembrane protein tyrosine pseudokinase | Cooperate with Fzd to localize Dvl | Expressed in cancer |